Early isolated V-lesion may not truly represent rejection of the kidney allograft

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F18%3A00077408" target="_blank" >RIV/00023001:_____/18:00077408 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68407700:21230/18:00324438 RIV/00216208:11110/18:10382779 RIV/00023736:_____/18:00012443

Výsledek na webu

<a href="http://www.clinsci.org/content/ppclinsci/132/20/2269.full.pdf" target="_blank" >http://www.clinsci.org/content/ppclinsci/132/20/2269.full.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1042/CS20180745" target="_blank" >10.1042/CS20180745</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Early isolated V-lesion may not truly represent rejection of the kidney allograft

Popis výsledku v původním jazyce

Intimal arteritis is known to be a negative prognostic factor for kidney allograft survival. Isolated v-lesion (IV) is defined as intimal arteritis with minimal tubulointerstitial inflammation (TI). Although the Banff classification assesses IV as T cell-mediated rejection (TCMR), clinical, and prognostic significance of early IV (early IV, eIV) with negative C4d and donor-specific antibodies (DSA) remains unclear. To help resolve if such eIV truly represents acute rejection, a molecular study was performed. The transcriptome of eIV (n= 6), T cell-mediated vascular rejection with rich TI (T cell-mediated vascular rejection, TCMRV, n= 4) and non-rejection histologic findings (n= 8) was compared using microarrays. A total of 310 genes were identified to be deregulated in TCMRV compared with eIV. Gene enrichment analysis categorized deregulated genes to be associated primarily with T-cells associated biological processes involved in an innate and adaptive immune and inflammatory response. Comparison of deregulated gene lists between the study groups and controls showed only a 1.7% gene overlap. Unsupervised hierarchical cluster analysis revealed clear distinction of eIV from TCMRV and showed similarity with a control group. Up-regulation of immune response genes in TCMRV was validated using RT-qPCR in a different set of eIV (n= 12) and TCMRV (n= 8) samples. The transcriptome of early IV (&lt; 1 month) with negative C4d and DSA is associated with a weak immune signature compared with TCMRV and shows similarity with normal findings. Such eIV may feature non-rejection origin and reflect an injury distinct from an alloimmune response. The present study supports use of molecular methods when interpreting kidney allograft biopsy findings.

Název v anglickém jazyce

Early isolated V-lesion may not truly represent rejection of the kidney allograft

Popis výsledku anglicky

Intimal arteritis is known to be a negative prognostic factor for kidney allograft survival. Isolated v-lesion (IV) is defined as intimal arteritis with minimal tubulointerstitial inflammation (TI). Although the Banff classification assesses IV as T cell-mediated rejection (TCMR), clinical, and prognostic significance of early IV (early IV, eIV) with negative C4d and donor-specific antibodies (DSA) remains unclear. To help resolve if such eIV truly represents acute rejection, a molecular study was performed. The transcriptome of eIV (n= 6), T cell-mediated vascular rejection with rich TI (T cell-mediated vascular rejection, TCMRV, n= 4) and non-rejection histologic findings (n= 8) was compared using microarrays. A total of 310 genes were identified to be deregulated in TCMRV compared with eIV. Gene enrichment analysis categorized deregulated genes to be associated primarily with T-cells associated biological processes involved in an innate and adaptive immune and inflammatory response. Comparison of deregulated gene lists between the study groups and controls showed only a 1.7% gene overlap. Unsupervised hierarchical cluster analysis revealed clear distinction of eIV from TCMRV and showed similarity with a control group. Up-regulation of immune response genes in TCMRV was validated using RT-qPCR in a different set of eIV (n= 12) and TCMRV (n= 8) samples. The transcriptome of early IV (&lt; 1 month) with negative C4d and DSA is associated with a weak immune signature compared with TCMRV and shows similarity with normal findings. Such eIV may feature non-rejection origin and reflect an injury distinct from an alloimmune response. The present study supports use of molecular methods when interpreting kidney allograft biopsy findings.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Clinical science

ISSN

0143-5221

e-ISSN

—

Svazek periodika

132

Číslo periodika v rámci svazku

20

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

16

Strana od-do

2269-2284

Kód UT WoS článku

000449102900009

EID výsledku v databázi Scopus

2-s2.0-85055618177